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Stellenwert der α1-Adrenozeptorblocker und 5α-Reduktaseinhibitoren

Monotherapie bei der Behandlung des benignen Prostatasyndroms

Importance of adrenoceptor blockers and alpha reductase inhibitors

Monotherapy for treatment of benign prostate syndrome

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Zusammenfassung

Bei Patienten mit moderaten bis schweren Symptomen des unteren Harntraktes (LUTS) stellt die medikamentöse Therapie die primäre konservative Therapieoption dar. Die zur Verfügung stehenden α1-Blocker sind bei Patienten mit moderaten bis schweren LUTS indiziert und können wegen ihres schnellen Wirkeintritts bei Patienten mit geringem Progressionsrisiko als Monotherapie eingesetzt werden. Trotz der Symptomverbesserung kann eine Krankheitsprogression nicht vermieden werden. 5α-Reduktaseinhibitoren (5ARI) eignen sich wegen ihres verzögerten Wirkeintritts primär nicht zur initialen Monotherapie. Mittel bis langfristig führen 5ARI zu einer Verbesserung der Symptome und der maximalen Harnflussrate und haben darüber hinaus – als einzige Substanzgruppe – einen positiven Effekt auf die Krankheitsprogression. Der Einsatz von 5ARI im Sinne einer BPS-Prävention ist zwar wissenschaftlich gut belegt jedoch ist dieser Ansatz nicht leitlinienkonform.

Abstract

Medicinal treatment is the primary conservative treatment option for patients with moderate to severe lower urinary tract symptoms (LUTS). Monotherapy with alpha-blockers may be a suitable option for patients with a low risk of progression and with moderate to severe LUTS due to the rapid onset of action. However, alpha-blockers do not have any impact on disease progression and 5-alpha-reductase inhibitors (5-ARIs) are not recommended as initial monotherapy due to a slow onset of action. In the medium and long term 5-ARIs have been shown to have a positive effect on symptoms and the maximum flow rate and are also the only substance group to have a positive effect on disease progression. The positive effects of 5-ARIs on prevention of benign prostate syndrome are based on scientific findings but the use is not yet recommended in any guidelines.

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Literatur

  1. Chapple CR, Roehrborn CG (2006) A shifted paradigm for the further understanding, evaluation, and treatment of lower urinary tract symptoms in men: focus on the bladder. Eur Urol 49(4):651–658

    Article  PubMed  Google Scholar 

  2. Berges R (2008) Epidemiology of benign prostatic syndrome. Associated risks and management data in German men over age 50. Urologe A 47(2):141–148

    Article  PubMed  CAS  Google Scholar 

  3. McConnell JD, Roehrborn CG, Bautista O et al (2003) The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 349(25):2387–2398

    Article  PubMed  CAS  Google Scholar 

  4. Berges R, Pientka L, Hoefner K et al (2009) Therapy of benign prostate syndrome (BPS): guidelines of the German Urologists (DGU). Urologe A 48(12):1503–1516

    Article  PubMed  CAS  Google Scholar 

  5. Strittmatter F, Walther S, Gratzke C et al (2012) Inhibition of adrenergic human prostate smooth muscle contraction by the inhibitors of c-Jun N-terminal kinase, SP600125 and BI-78D3. Br J Pharmacol 166(6):1926–1935

    Article  PubMed  CAS  Google Scholar 

  6. Strittmatter F, Walther S, Gratzke C et al (2012) Activation of protein kinase B/Akt by alpha1-adrenoceptors in the human prostate. Life Sci 90(11–12):446–453

    Google Scholar 

  7. Strittmatter F, Gratzke C, Walther S et al (2011) Alpha1-adrenoceptor signaling in the human prostate involves regulation of p38 mitogen-activated protein kinase. Urology 78(4):969

    Article  PubMed  Google Scholar 

  8. Bauer RM, Strittmatter F, Gratzke C et al (2011) Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the human prostate. Urol Int 86(4):427–433

    Article  PubMed  CAS  Google Scholar 

  9. Kortmann BB, Floratos DL, Kiemeney LA et al (2003) Urodynamic effects of alpha-adrenoceptor blockers: a review of clinical trials. Urology 62(1):1–9

    Article  PubMed  Google Scholar 

  10. Murata S, Taniguchi T, Takahashi M et al (2000) Tissue selectivity of KMD-3213, an alpha(1)-adrenoreceptor antagonist, in human prostate and vasculature. J Urol 164(2):578–583

    Article  PubMed  CAS  Google Scholar 

  11. Barendrecht MM, Abrams P, Schumacher H et al (2008) Do alpha1-adrenoceptor antagonists improve lower urinary tract symptoms by reducing bladder outlet resistance? Neurourol Urodyn 27(3):226–230

    Article  PubMed  CAS  Google Scholar 

  12. Andersson KE, Gratzke C (2007) Pharmacology of alpha1-adrenoceptor antagonists in the lower urinary tract and central nervous system. Nat Clin Pract Urol 4(7):368–378

    Article  PubMed  CAS  Google Scholar 

  13. Strittmatter F, Hedlund P (2011) Silodosin:pharmacological and clinical features. Aging Health 7(1):45–57

    Article  CAS  Google Scholar 

  14. Djavan B, Chapple C, Milani S et al (2004) State of the art on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Urology 64(6):1081–1088

    Article  PubMed  Google Scholar 

  15. Kerrebroeck P van, Jardin A, Laval KU, van Cangh P (2000) Efficacy and safety of a new prolonged release formulation of alfuzosin 10 mg once daily versus alfuzosin 2.5 mg thrice daily and placebo in patients with symptomatic benign prostatic hyperplasia. ALFORTI Study Group. Eur Urol 37(3):306–313

    Article  PubMed  Google Scholar 

  16. MacDonald R, Wilt TJ (2005) Alfuzosin for treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia: a systematic review of efficacy and adverse effects. Urology 66(4):780–788

    Article  PubMed  Google Scholar 

  17. Wilt TJ, Howe RW, Rutks IR, MacDonald R (2002) Terazosin for benign prostatic hyperplasia. Cochrane Database Syst Rev 4:CD003851

    PubMed  Google Scholar 

  18. Wilt TJ, Mac Donald R, Rutks I (2003) Tamsulosin for benign prostatic hyperplasia. Cochrane Database Syst Rev 1:CD002081

    PubMed  Google Scholar 

  19. Michel MC, de la Rosette JJ (1998) Comparison of tamsulosin efficacy in subgroups of patients with lower urinary tract symptoms. Prostate Cancer Prostatic Dis 1(6):332–335

    Article  PubMed  CAS  Google Scholar 

  20. Nickel JC, Sander S, Moon TD (2008) A meta-analysis of the vascular-related safety profile and efficacy of alpha-adrenergic blockers for symptoms related to benign prostatic hyperplasia. Int J Clin Pract 62(10):1547–1559

    Article  PubMed  CAS  Google Scholar 

  21. Barendrecht MM, Koopmans RP, de la Rosette JJ, Michel MC (2005) Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: the cardiovascular system. BJU Int 95(Suppl 4):19–28

    Article  PubMed  CAS  Google Scholar 

  22. Chapple CR, Montorsi F, Tammela TL et al (2011) Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe. Eur Urol 59(3):342–352

    Article  PubMed  CAS  Google Scholar 

  23. Chang DF, Campbell JR (2005) Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg 31(4):664–673

    Article  PubMed  Google Scholar 

  24. Andriole G, Bruchovsky N, Chung LW et al (2004) Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol 172(4 Pt 1):1399–1403

    Article  PubMed  CAS  Google Scholar 

  25. Naslund MJ, Miner M (2007) A review of the clinical efficacy and safety of 5alpha-reductase inhibitors for the enlarged prostate. Clin Ther 29(1):17–25

    Article  PubMed  CAS  Google Scholar 

  26. Nickel JC, Roehrborn C, Montorsi F et al (2011) Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS). BJU Int 108(3):388–394

    Article  PubMed  CAS  Google Scholar 

  27. Lepor H, Williford WO, Barry MJ et al (1996) The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med 335(8):533–539

    Article  PubMed  CAS  Google Scholar 

  28. Kirby RS, Roehrborn C, Boyle P et al (2003) Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 61(1):119–126

    Article  PubMed  Google Scholar 

  29. Roehrborn CG, Lukkarinen O, Mark S et al (2005) Long-term sustained improvement in symptoms of benign prostatic hyperplasia with the dual 5alpha-reductase inhibitor dutasteride: results of 4-year studies. BJU Int 96(4):572–577

    Article  PubMed  Google Scholar 

  30. Roehrborn CG, Siami P, Barkin J et al (2010) The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol 57(1):123–131

    Article  PubMed  Google Scholar 

  31. Roehrborn CG, Barkin J, Siami P et al (2011) Clinical outcomes after combined therapy with dutasteride plus tamsulosin or either monotherapy in men with benign prostatic hyperplasia (BPH) by baseline characteristics: 4-year results from the randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) trial. BJU Int 107(6):946–954

    Article  PubMed  CAS  Google Scholar 

  32. Roehrborn CG (2008) BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU Int 101(Suppl 3):17–21

    Article  PubMed  Google Scholar 

  33. Barkin J, Guimarães M, Jacobi G et al (2003) Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride. Eur Urol 44(4):461–466

    Article  PubMed  CAS  Google Scholar 

  34. Nickel JC, Barkin J, Koch C et al (2008) Finasteride monotherapy maintains stable lower urinary tract symptoms in men with benign prostatic hyperplasia following cessation of alpha blockers. Can Urol Assoc J 2(1):16–21

    PubMed  Google Scholar 

  35. Thompson IM, Goodman PJ, Tangen CM et al (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349(3):215–224

    Article  PubMed  CAS  Google Scholar 

  36. Parsons JK, Schenk JM, Arnold KB et al (2012) Finasteride reduces the risk of incident clinical benign prostatic hyperplasia. Eur Urol 62(2):234–241

    Article  PubMed  CAS  Google Scholar 

  37. Andriole GL, Bostwick DG, Brawley OW et al (2010) Effect of dutasteride on the risk of prostate cancer. N Engl J Med 362(13):1192–1202

    Article  PubMed  CAS  Google Scholar 

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Interessenskonflikt

Der korrespondierende Autor weist für sich und seine Koautoren auf folgende Beziehungen hin: CG war tätig für Bayer Healthcare, Sanofi-Aventis, Rottapharm Madaus, Lilly, Recordati und MSD; SM war und ist tätig für Bayer, Madaus, Lilly, MSD, Pfizer, Astellas und GSK.

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Authors and Affiliations

  1. Urologische Klinik und Poliklinik, Klinikum der Universität München-Großhadern, Marchioninistr. 15, 81377, München, Deutschland

    F. Strittmatter, C.G. Stief & C. Gratzke

  2. Abteilung für Urologie, Donauspital Wien, Wien, Österreich

    S. Madersbacher

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  1. F. Strittmatter
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  2. S. Madersbacher
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  3. C.G. Stief
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  4. C. Gratzke
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Correspondence to F. Strittmatter.

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Strittmatter, F., Madersbacher, S., Stief, C. et al. Stellenwert der α1-Adrenozeptorblocker und 5α-Reduktaseinhibitoren. Urologe 52, 197–203 (2013). https://doi.org/10.1007/s00120-012-3086-0

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